The cornea consists of the three layers of epithelium, stroma and endothelium; the corneal endothelium is a single cell layer located on the innermost side of the cornea, working to retain the water content of the cornea and maintain the transparency. Corneal endothelial cells are poor in proliferative capability in vivo; when some corneal endothelial cells are damaged, neighboring cells elongate to fill in the damaged area. For this reason, corneal endothelial cells, once damaged, become less dense and no longer capable of maintaining the transparency. This pathologic condition is called bullous keratopathy, causing serious visual impairment.
As a factor known to allow corneal endothelial cells with low proliferative capability to proliferate, bFGF is used to culture corneal endothelial cells in vitro. Available in the past literature is a report on an attempt to accelerate corneal endothelial cell proliferation by administration of bFGF solution into the anterior chamber in vivo (non-patent document 1). However, the aqueous humor is constantly produced and excreted, 20% of the aqueous humor being exchanged in 1 hour. To allow bFGF to act on corneal endothelial cells for a long time, an appropriate carrier that allows the drug to be released in a sustained manner is needed. Meanwhile, since bFGF is known to act as a potent neovascularization factor in a variety of organs, there is a demand for establishing a method of appropriately administering bFGF and amounts administered such that such various side effects are suppressed to the minimum levels and the therapeutic effect is maximized in corneal endothelium regenerative medicine.
The present inventors found that gelatin hydrogel (crosslinked gelatin gel) is useful as a good carrier capable of releasing protein in a sustained manner, and have already developed a bFGF sustained-release gelatin hydrogel (bFGF-containing crosslinked gelatin gel) preparation incorporating this carrier. Although this bFGF sustained-release gelatin hydrogel preparation is highly useful in accelerating neovascularization and treating bone fractures, no report has been presented to date on the application thereof to the acceleration of corneal endothelial cell proliferation (patent documents 1-4, non-patent documents 2 and 3).